title: Rosiglitazone decreases bone mass and bone marrow fat.
abstract: BACKGROUND
  Activation of peroxisome proliferator-activated receptor-γ is believed to promote adipocyte development from mesenchymal stem cells in the bone marrow at the expense of osteoblasts, leading to decreased bone mineral density (BMD) and increased marrow fat.
  
  
  OBJECTIVE
  The objective of the study was to examine the effect of the peroxisome proliferator-activated receptor-γ agonist, rosiglitazone, on BMD assessed by dual-energy x-ray absorptiometry in 53 healthy postmenopausal women and spine bone marrow fat assessed by magnetic resonance imaging proton spectroscopy.
  
  
  METHODS
  This was a 14-wk prospective, double-blind, randomized, placebo-controlled trial.
  
  
  METHODS
  The study was conducted in the general community.
  
  
  METHODS
  Fifty-three healthy postmenopausal women participated in the study.
  
  
  METHODS
  Intervention included rosiglitazone tablets of 8 mg/d.
  
  
  METHODS
  The primary end point was a change in BMD.
  
  
  RESULTS
  At the femoral neck, BMD decreased by 1.34 ± 0.60% (mean ± sem) in the rosiglitazone group, whereas BMD increased by 0.28 ± 0.56% in the placebo group (P = 0.055). At the lumbar spine, BMD decreased by 1.03 ± 0.34% in the rosiglitazone group and 0.42 ± 0.35% in the placebo group (P = 0.22). The bone resorption marker carboxy-terminal telopeptide increased by 20.4 ± 7.7% (mean ± sem) in the rosiglitazone group and decreased by 7.1 ± 4.7% in the placebo group (P = 0.003). Spine fat decreased by 13.5 ± 5.5% (mean ± sem) in the rosiglitazone group and increased by 6.8 ± 7.4% in the placebo group (P = 0.056).
  
  
  CONCLUSIONS
  Contrary to what was expected, spine fat decreased during rosiglitazone treatment. Furthermore, rosiglitazone treatment resulted in uncoupling of bone resorption and formation leading to bone loss. Our data suggest that the bone marrow osteoblast-adipocyte relationship is more complex than was assumed and that the two cell types can be independently affected.
authors.affiliation: Department of Endocrinology and Internal Medicine, THG, Aarhus University Hospital, Tage-Hansens Gade 2, DK-8000 Aarhus C, Denmark. torbhars@rm.dk
authors.forename: Torben
authors.initials: T
authors.lastname: Harsløf
authors.forename: Louise
authors.initials: L
authors.lastname: Wamberg
authors.forename: Louise
authors.initials: L
authors.lastname: Møller
authors.forename: Hans
authors.initials: H
authors.lastname: Stødkilde-Jørgensen
authors.forename: Steffen
authors.initials: S
authors.lastname: Ringgaard
authors.forename: Steen B
authors.initials: SB
authors.lastname: Pedersen
authors.forename: Bente L
authors.initials: BL
authors.lastname: Langdahl
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D015415:Biomarkers; D015519:Bone Density / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism*; D001862:Bone Resorption / Q000378:metabolism; D001842:Bone and Bones / Q000033:anatomy & histology*; D024042:Collagen Type I / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D008875:Middle Aged; D047495:PPAR gamma / Q000819:agonists*; D010455:Peptides / Q000097:blood; D017698:Postmenopause / Q000502:physiology; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D010455:Peptides; D045162:Thiazolidinediones; C052929:collagen type I trimeric cross-linked peptide; D000077154:Rosiglitazone